Rong Ju1, Wei Wu1, Juan Fei2, Yufeng Qin3, Qiuqin Tang2, Di Wu3, Yankai Xia3, Jie Wu4, Xinru Wang5. 1. Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Med 2. Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. 3. Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. 4. Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China xrwang@njmu.edu.cn jie.wuyale@gmail.com. 5. Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China Department of Gynaecology and ObstetricsNanjing Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing 211100, ChinaState Key Laboratory of Reproductive MedicineSchool of Public Health, Institute of Toxicology, Nanjing Medical University, 101 Longmian Road, Nanjing 211166, ChinaKey Laboratory of Modern ToxicologyNanjing Medical University, Ministry of Education, Nanjing 211166, ChinaState Key Laboratory of Reproductive MedicineWuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, ChinaJiangsu Provincial Center for Disease Control and PreventionNanjing 210009, ChinaState Key Laboratory of Reproductive MedicineNanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, ChinaState Key Laboratory of Reproductive MedicineDepartment of Gynaecology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China xrwang@njmu.edu.cn jie.wuyale@gmail.com.
Abstract
OBJECTIVE: To assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population. DESIGN: A case-control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS. METHODS: In this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method. RESULTS AND CONCLUSIONS: We found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19-2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07-2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.
OBJECTIVE: To assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population. DESIGN: A case-control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS. METHODS: In this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method. RESULTS AND CONCLUSIONS: We found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19-2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07-2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.
Authors: Ani Manichaikul; Lauren C Peres; Xin-Qun Wang; Mollie E Barnard; Deanna Chyn; Xin Sheng; Zhaohui Du; Jonathan Tyrer; Joseph Dennis; Ann G Schwartz; Michele L Cote; Edward Peters; Patricia G Moorman; Melissa Bondy; Jill S Barnholtz-Sloan; Paul Terry; Anthony J Alberg; Elisa V Bandera; Ellen Funkhouser; Anna H Wu; Celeste Leigh Pearce; Malcom Pike; Veronica Wendy Setiawan; Christopher A Haiman; Julie R Palmer; Loic LeMarchand; Lynne R Wilkens; Andrew Berchuck; Jennifer A Doherty; Francesmary Modugno; Roberta Ness; Kirsten Moysich; Beth Y Karlan; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Kate Lawrenson; Simon Gayther; Thomas A Sellers; Paul Pharoah; Joellen M Schildkraut Journal: Int J Cancer Date: 2019-10-08 Impact factor: 7.316
Authors: Michael W O'Reilly; Punith Kempegowda; Mark Walsh; Angela E Taylor; Konstantinos N Manolopoulos; J William Allwood; Robert K Semple; Daniel Hebenstreit; Warwick B Dunn; Jeremy W Tomlinson; Wiebke Arlt Journal: J Clin Endocrinol Metab Date: 2017-09-01 Impact factor: 5.958